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Predictors of Survival in Patients with Sarcoma Admitted to the Intensive

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Predictors of Survival in Patients with Sarcoma Admitted to the Intensive Gupta et al. Clin Sarcoma Res (2016) 6:12 DOI 10.1186/s13569-016-0051-5 Clinical Sarcoma Research RESEARCH Open Access Predictors of survival in patients with sarcoma admitted to the intensive care unit Rohan Gupta1, Neda Heshami1, Chouhan Jay1, Naveen Ramesh2, Juhee Song3, Xiudong Lei3, Erfe Jean Rose4, Kristen Carter5, Dejka M. Araujo5, Robert S. Benjamin5, Shreyaskumar Patel5, Joseph L. Nates4 and Vinod Ravi5* Abstract Background: Advances in treatment of sarcoma patients has prolonged survival but has led to increased disease- or treatment-related complications resulting in greater number of admissions to the intensive care unit (ICU). Survival and long-term outcome information about such critically ill patients with sarcoma is unknown. Methods: The primary objective of the study was to determine the ICU and post-ICU survival rates of critically ill sarcoma patients. Secondary objectives included determining the modifiable and non-modifiable predictors of poor survival. We performed a retrospective chart review of sarcoma patients admitted to the ICU at The University of Texas MD Anderson Cancer Center between January 1, 2005, and December 31, 2012. Main outcome measures were ICU mortality, in-hospital mortality and 1, 2, and 6-month survival rates. Covariates such as histological diagnosis, disease characteristics, chemotherapy use, Charlson comorbidity index, Sequential Organ Failure Assessment (SOFA) scores, and clinical findings leading to ICU admission were analyzed for their effects on survival. Results: We identified 172 admissions over the 8-year study period hat met our inclusion criteria. The study popula- tion was 45.9 % males with a median age of 52 years. The most common sarcoma subgroups were high-grade unclas- sified sarcoma (25 %) and bone tumors (17.4 %). The ICU mortality rate was 23.3 % (95 % confidence interval [CI], 16.9–29.6 %), and an additional 6.4 % of patients died before hospital discharge (95 % CI, 22.9–37.1 %). 6-month OS rates were 41 %. The median SOFA scores on admission were 6 (inter quartile range (IQR), 3.5–9) in ICU survivors and 10 (IQR, 6.5–14) in ICU non-survivors. Increase in SOFA scores 6 led to poor outcomes (ICU survival 13.3 %, OS 6.7 %). Charlson comorbidity index (HR 1.139, 95 % CI 1.023–1.268, p≥ 0.02) and discharge SOFA scores (HR 1.210, 95 % CI 1.141–1.283, p < 0.0001) correlated with overall survival. = Conclusions: Our results suggest that patients that are admitted to the ICU for respiratory failure, cardiac arrest, sep- tic shock, acute renal failure or acidosis and also have a high SOFA score with subsequent worsening in the ICU have poor prognosis. Based on the retrospective data which needs further validation we can recommend that judicious approach should be taken in patients with predictors of poor survival before subjecting them to aggressive treatment. Keywords: Cancer, Sarcoma, ICU, Survival, SOFA *Correspondence: [email protected] 5 Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd # 450, Houston, TX 77030, USA Full list of author information is available at the end of the article © 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Gupta et al. Clin Sarcoma Res (2016) 6:12 Page 2 of 12 Background of patients admitted to the ICU with sarcoma during the Sarcomas are a rare, histologically and behaviorally study period. Secondary outcomes were in-hospital mor- diverse group of malignant connective tissue tumors that tality and 1, 2, and 6-month survival rates, which were make up approximately 1 % of all adult malignancies and defined by similar means. Overall survival (OS) for each 12 % of pediatric cancers [1, 2]. As a result of the substan- patient was measured from the time of initial ICU admis- tial progress made in the past 2 decades in understand- sion to the last date of contact or death. We defined ICU ing the behavior and molecular pathogenesis of sarcoma, survival as short-term or acute survival and 6-month sur- new therapies have been developed. Advances in treat- vival as long-term survival. Median follow-up time was ment may prolong survival but can lead to increased calculated from the date of ICU admission. disease- or treatment-related complications requiring Patient’s current and previous chemotherapy regimens aggressive critical care. Due to the rarity of this class of were examined to evaluate the impact of various chemo- tumors, the survival of critically ill sarcoma patients has therapy treatments on survival. Tumor burden was noted not been well studied. by recording the various sites of metastasis, such as head The treatment of such patients requires a multidisci- and neck, musculoskeletal, heart, lung, liver, gastrointes- plinary approach, with coordination among oncologists, tinal tract, and spleen. The Charlson comorbidities index critical care physicians, consulting services, ancillary (CCI) was used to assess the role of serious comorbid dis- staff, and patients’ families. Despite the availability of ease in the survival of patients in the study [9]. advanced life support devices in intensive care centers in Clinical findings present at the time of ICU admis- the United States, it is difficult for both patients and phy- sion were recorded to assess acute illness (definitions in sicians to objectively determine the effect of such heroic parentheses). Variables recorded included acute renal measures on prognosis or quality of life. Studies up to the failure, anemia, thrombocytopenia, pancytopenia, 1990s had shown that among all diseases, patients with hemorrhage (including bleeding from gastrointestinal cancer had the lowest intensive care unit (ICU) survival tract), lactic acidosis, heart failure, pulmonary embo- rates, and the majority of these patients died soon after lism, respiratory failure (use of noninvasive or invasive their hospital discharge [3–5]. However, over the past mechanical ventilation), cardiac arrest, atrial fibrillation, two decades, the approach to treatment in such cases cardiac dysrhythmia, pneumonia, septic shock, hypoten- has been shifting. Some studies have shown that patients sion (systolic blood pressure <100 or on vasopressors), lacking predictors of poor survival outcomes are consid- hypertension, neutropenic fever (absolute neutrophil ered as good candidates for aggressive therapy [6–8]. count <1500), altered mental status, and malnutrition The primary objective of our study was to determine (patient on feeding tube or total parental nutrition). the ICU and post-ICU survival rates of critically ill sar- Severity of illness at the time of ICU admission was coma patients. Secondary objectives included determin- measured by Sequential Organ Failure Assessment ing the modifiable and nonmodifiable predictors of poor (SOFA) scores. Maximum SOFA scores and discharge survival. SOFA scores were also obtained to track the patients’ progress while they were in the ICU. Change in SOFA Methods scores were calculated by subtracting the admission Patient population SOFA scores from the maximum SOFA scores. Organ After obtaining institutional review board approval, we failure at the time of ICU admission was determined by retrospectively reviewed the electronic medical records an admission SOFA score ≥2 per organ system. The total of 212 critically ill patients with sarcoma who had been number of organ failures was calculated for each patient. admitted to the ICU at The University of Texas MD Anderson Cancer Center between January 1, 2006, and Analysis December 31, 2012. For the purpose of this analysis, we Patient characteristics were tabulated and compared limited the study population to patient’s first ICU admis- between groups by using the Chi square test or Fisher sion only. We also excluded from the study population exact test as appropriate for categorical variables and by patients who had been admitted to the ICU for periop- the nonparametric Wilcoxon rank sum test for continu- erative care. ous variables. A multivariate logistic regression model was fitted to examine the relationship between death in Study design the ICU and clinical characteristics. Patients who were This retrospective study was designed to identify predic- lost to follow-up or alive were censored at their dates of tors of poor survival that contribute to ICU mortality. last contact. The Kaplan–Meier product limit method was ICU mortality was defined as the percentage of patients used to estimate the survival outcomes of all patients by with sarcoma who died in the ICU among total number groups; the log-rank statistic was used to compare groups. Gupta et al. Clin Sarcoma Res (2016) 6:12 Page 3 of 12 Cox proportional hazards models were fitted to deter- non-survivors. Patients with admission SOFA scores of mine the association of patient and clinical characteristics 11 or more had a lower ICU survival rate than did those with OS. Variables that had significant univariate log- with scores less than 11 (45.7 vs 80 % or more) (Table 2). rank p values were candidates for the multivariate model. An increase of 6 or more in the SOFA score from the time Results were expressed in hazard ratios (HRs), odds ratios of admission significantly affected short- (ICU survival (ORs) and 95 % confidence intervals (CIs). p values of less 13.3 %) and long-term outcomes (OS 6.7 %) (Table 3). than 0.05 were considered statistically significant; all tests Multivariate logistic regression model for death in the were two-sided. Statistical analyses were carried out by ICU showed that SOFA admission score (OR 1.23, 95 % using SAS 9.4 (SAS Institute Inc., Cary, NC) and S-Plus CI 1.12–1.35, p < 0.0001) was associated with death 8.2 (TIBCO Software Inc, Palo Alto, CA, USA).
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